Amylin
| islet amyloid polypeptide | |||||||
|---|---|---|---|---|---|---|---|
| File:Amylin IAPP structure.png caption | |||||||
| Identifiers | |||||||
| Symbol | IAPP | ||||||
| NCBI gene | 3375 | ||||||
| HGNC | 5329 | ||||||
| OMIM | 147940 | ||||||
| PDB | 2G48 | ||||||
| RefSeq | NM_000415 | ||||||
| UniProt | P10997 | ||||||
| Other data | |||||||
| Locus | Chr. 12 p12.3-p12.1 | ||||||
| |||||||
Amylin, or Islet Amyloid Polypeptide (IAPP), is a 37-residue peptide hormone secreted by pancreatic β-cells at the same time as insulin (in a roughly 100:1 ratio).
Structure
The human form of IAPP has the amino acid sequence KCNTATCATQRLANFLVHSSNNFGAILSSTNVGSNTY, with a disulfide bridge between cysteine residues 2 and 7. The peptide is secreted from the pancreas into the blood circulation and eventually excreted by the kidneys. IAPP is capable of forming amyloid fibrils in vitro. Within the fibrillization reaction, the early prefibrillar structures are extremely toxic to insuloma cells cultures. Later amyloid fibril structures also seem to have some cytotoxic effect on cell cultures. Rats and mice have proline residues that prevent the formation of amyloid fibrils.
Function
Amylin functions as part of the endocrine pancreas and contributes to glycemic control. Although amylin's complete function may not yet be known, it has been shown to slow gastric emptying, promote satiety, inhibit secretion of glucagon during hyperglycemia, and therein reduce the total insulin demand.[1][2] As insulin lowers blood glucose and glucagon raises blood glucose, amylin supports the stability of blood glucose levels in effect by slowing the rate that digested glucose enters the bloodstream.
Rodent amylin knockouts are known to fail to achieve the normal anorexia following food consumption. Because it is an amidated peptide, like many neuropeptides, it is believed to be responsible for the anorectic effect.
History
IAPP was identified independently by two groups as the major component of diabetes-associated islet amyloid deposits in 1987.[3][4]
Pharmacology
Synthetic amylin, or pramlintide (brand name Symlin) was recently approved for adult use in patients with diabetes mellitus type 1. Insulin and pramlintide, injected separately but both before a meal, work together to control the post-prandial glucose excursion. (Amylin Pharmaceuticals, Inc, symlin, retrieved 2007-05-05)
Receptors
There appears to be at least three distinct receptor complexes that bind with high affinity to amylin. All three complexes contain the calcitonin receptor at the core, plus one of three Receptor activity-modifying proteins, RAMP1, RAMP2, or RAMP3.[5]
References
- ^ Ratner RE, Dickey R, Fineman M, Maggs DG, Shen L, Strobel SA, Weyer C, Kolterman OG (2004). "Amylin replacement with pramlintide as an adjunct to insulin therapy improves long-term glycaemic and weight control in Type 1 diabetes mellitus: a 1-year, randomized controlled trial". Diabet Med. 21 (11): 1204–12. PMID 15498087.
{{cite journal}}: CS1 maint: multiple names: authors list (link) - ^ http://www.symlin.com
- ^ Cooper GJ, Willis AC, Clark A, Turner RC, Sim RB, Reid KB (1987). "Purification and characterization of a peptide from amyloid-rich pancreases of type 2 diabetic patients". Proc Natl Acad Sci USA. 84 (23): 8628–32. PMID 3317417.
{{cite journal}}: CS1 maint: multiple names: authors list (link) - ^ Westermark P, Wernstedt C, Wilander E, Hayden DW, O'Brien TD, Johnson KH (1987). "Amyloid fibrils in human insulinoma and islets of Langerhans of the diabetic cat are derived from a neuropeptide-like protein also present in normal islet cells". Proc Natl Acad Sci USA. 84 (11): 3881–3885. PMID 3035556.
{{cite journal}}: CS1 maint: multiple names: authors list (link) - ^ Hay DL, Christopoulos G, Christopoulos A, Sexton PM (2004). "Amylin receptors: molecular composition and pharmacology". Biochem Soc Trans. 32 (5): 865–7. PMID 15494035.
{{cite journal}}: CS1 maint: multiple names: authors list (link)
Notes
- ^ Chronic Oxidative Stress as a Central Mechanism for Glucose Toxicity in Pancreatic Islet Beta Cells in Diabetes. JBC Vol. 279, Issue 41, 42351-42354, October 8, 2004
- ^ Amyloidosis in cats from Petdiabetes wiki.
External links
- amylin at the U.S. National Library of Medicine Medical Subject Headings (MeSH)
- PDB entry 1KUW for amylin
- Shen et al. "Structures of human insulin-degrading enzyme reveal a new substrate recognition mechanism." (substrates include amylin), PMID 17051221
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